Stem cell research sheds light on new 'molecular road' to Alzheimer's disease
Alzheimer's disease (AD) varies widely in its age of onset, presentation and severity. Recently, the SORL1 gene has received increased attention since variations in this gene have been associated with both early and late onset AD. However, little is known about how damage to SORL1 leads to disease.
Using stem cells from patients with AD, investigators from Brigham and Women's Hospital, a founding member of the Mass General Brigham health care system, found that loss of normal SORL1 function leads to a reduction in two key proteins known to be involved in AD and which play an essential role in the neurons of healthy individuals. Their results, published in Cell Reports, suggest a potential new strategy for AD treatment, especially for patients not responsive to existing therapies.
Key neurological features of AD, including the abundance of amyloid-beta plaques in the brain, also vary across individuals.
Brigham researchers played a leadership role in understanding the molecular and genetic basis for AD, including making key discoveries related to the amyloid protein.
In this new study, the researchers utilized a stem-cell based approach that examined natural genetic variability in AD patients to gain insight into an alternative pathway driving disease. The researchers used CRISPR technologies to remove the SORL1 gene from progenitor stem cells. They programmed the stem cells to differentiate into four different kinds of brain cells to examine the impact of removing SORL1 on each cell type.
The researchers verified their lab-based results by examining natural genetic variation in SORL1 expression in the brain tissue of 50 members of the cohorts, finding again that lower SORL1 activity in neurons was correlated with reduced APOE and CLU in these people.
https://medicalxpress.com/news/2023-08-stem-cell-molecular-road-alzheimer.html
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